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Biologic indices of heterogeneity in schizophrenia: Relationship to psychopathology and treatment outcome
289 4. A. Pietzcker
et al., Pharmacopsychiat.
Monitoring
19:161-
166,19%.
service implementation
W.A. Hargreaves*,
T. Chouljian,
C. Coppolino,
in controlled
services trials
R. Hughes, R. Mance, J. Wade
Department of Psychiatry, University of California, SFGH Room 7M36, San Francisco, CA 94143-0852, USA
Manual-specified pharmacological and psychosocial treatment and other services are the norm for well designed controlled trials of interventions for patients with schizophrenia. Increased attention is being given to monitoring the actual implementation of services in controlled studies. We examined the ability of a simple instrument, the Community Program Philosophy Scale (CPPS), to detect differences among the five sites of the NIMH Treatment Strategies in Schizophrenia cooperative study, and between these five sites and a large group of other community programs that provide services to severely and persistently disabled persons with schizophrenia and other serious mental disorders. The CPPS was administered independently to several staff with client contact in each program. The 80 items of the CPPS form 20 4-item subscales that each have good internal consistency. A group of 12 subscales distinguished strongly among the set of comparison programs (subscales Outreach Orientation, Housing Assistance, Referral Advocacy, Emergency Access, Linking to Entitlements, Team vs Primary Therapist model, Longitudinality of Service, Family Orientation, Interest in Severely Mentally Ill Clients, De-emphasis of Psychotherapy, Substance Abuse Orientation, and Vocational Emphasis). Relative to the comparison programs, the cooperative study sites were tightly clustered on most of these subscales. The CPPS nevertheless showed sufficient sensitivity to detect statistically significant differences among the 5 cooperative study sites on 8 of the 20 subscales. It will be of interest to see whether these relatively subtle differences among the study sites have any relation to the relative cost effectiveness of the six treatments being compared, when this randomized controlled trial is completed.
Life events and prodromal
symptoms
in schizophrenia
M.I. Herz*, W.M. Glazer, M.A. Mostert Department of Psychiatry, SUNYat Buffalo, 462
GriderStreet, Buffalo, NyJ4215, USA.
We conducted a double-blind placebo controlled study of 101 schizophrenic outpatients comparing intermittent (antipsychotic medication given only when early symptoms of relapse appear) with maintenance medication. Since this was a double-blind study, when prodromal symptoms appeared, patients in both groups were given active antipsychotic medication openly. A variety of rating scales were administered at baseline, cross-sectionally every 6 months and during prodromal episodes, including measures of symptomatology, role functioning, life events, and family burden. This paper will describe the most frequent life events and prodromal symptoms found in the course of the study. It will also compare the frequency of life events and subjective reaction to them at baseline with those reported prior to the appearance of prodromal symptoms. The number of relapses and hospitalizations in each group will be reported. Knowledge about typical prodromal symptoms and life events which precede prodromal episodes should be of benefit in helping to prevent relapse and rehospitalization in schizophrenia.
Biologic indices of heterogeneity in schizophrenia: psychopathology and treatment outcome J. Lieberman*,
Relationship
to
D. Mayerhoff, A. Loebel, G. Degreef, D. Levy, J. Alvir
HilIside Hospital, Deparlment of Psychiatry, P.O. box 38, Glen Oaks, NY 11004, USA.
Biologic studies have consistently demonstrated brain morphologic, neurochemical and psychophysiologic pathology in schizophrenia. Efforts to determine the pathogenesis of these deficits and relate them to the phenomenology and course of schizophrenia in an effort to reduce the clinical heterogeneity of the disease, however, have been largely unsuccessful. Even the most robust biological abnormalities have been questioned
290 as to whether they reflect true pathology or the effects of illness chronicity, institutionalization and pharmacologic treatment. Consequently, we have initiated a study of never treated patients in their first episode of illness in a prospective longitudinal design to characterize biologic deficits and determine their clinical significance. Seventy-two patients (63% male, mean age 23 2 5.7 years) were ascertained when admitted to hospital for their first episode of schizophrenia and prior to neuroleptic treatment. Patients underwent clinical evaluation, MRI, methylphenidate challenge test and smooth pursuit eye movement exams under controlled conditions using standardized procedures. Patients received standardized treatment and were followed for up to three years with clinical evaluations. Rates of pathobiology for the measures used were: abnormal brain morphology 30%, psychotogenic response to methyl 61%, abnormal SPEM 43% (all rates were stat. sign. greater than normal control groups). Eighty-four percent of subjects achieved remission in a mean (SE)/median (SE) of 35.7 (7.4)/13 (3.1) weeks. The global outcomes of the sample were: 20% excellent, 21% good, 43% fair, 16% poor. Individual biologic abnormalities were significantly associated with poorer treatment response and outcome. When the combined effects of the biologic variables on treatment outcome were examined, the strength of the correlations (r) increased from .45 to 8 (P = .Ol). These and further results on the relationships between the biologic variables and psychopathology and treatment outcome will be presented and discussed.
Correlates
of course and outcome in first-episode
A. Loebel*, J. Lieberman,
schizophrenia
D. Mayerhoff, D. Jody, S. Szymanski, S. Geisler, M. Borenstein,
Hillside Hospital, Research Department, P.O. Box 38, Glen Oaks, Ny11004,
J. Ma Alvir
USA.
Various sociodemographic, phenomenologic and pathobiologic features have been associated with schizophrenic outcome. Major determinants of outcome remain unclear. Previous studies have been limited by retrospective evaluations, variations in illness chronicity and medication status, and heterogeneity in diagnosis and treatment, among other factors. In order to determine the relative contributions of premorbid functioning, age and mode of onset, and illness duration on various outcome measures, we studied 57 treatment-naive, first-episode schizophrenic patients as part of a larger, ongoing, prospective outcome study. Mean (5 S.D.) age on admission was 23.9 (* 5.7) years with a range of 14 to 40 years. The sample consisted of 41(72%) schizophrenics and 16 (28%) schizoaffective patients, diagnosed according to Research Diagnostic Criteria (RDC). Mean duration of symptoms on index admission was 1.4 years. All patients received structured diagnostic interviews and follow-up clinical and psychobiological assessments at regular intervals over a 3 year period. Standardized treatment algorithms were uniformly employed throughout their course. All patients were diagnostically assessed and subsequently followed by the same investigators. We propose that illness duration and premorbid adjustment in child and adolescent age ranges. Impaired premorbid adjustment was associated with shorter illness duration (prior to index hospitalization), but did not predict type of presenting psychopathology (positive psychotic vs negative symptoms). Using a Cox Proportional Hazards model of survival analysis, greater illness duration was found to predict increased time to remission in a younger age range (14 -24 years). Further potential predictors of course and outcome including age and mode of onset, illness subtype and severity, and presence of early deficit state symptoms, will be presented. Pathophysiologic implications of the lack of an illness duration effect in the older age range (25 -40 years) will be discussed. We conclude that early intervention in the course of schizophrenic illness, particularly in younger, premorbidly impaired patients, may assist in improving overall treatment outcome in first-episode schizophrenia. Further research will need to confirm and extend findings on the role of sociodemographic and clinical variables, as well as neuropsychologic and cerebral morphologic status of first-episode patients, in course and outcome of schizophrenia.
Plasma level monitoring
of depot neuroleptics
S.R. Marder*, T. Van Putten, M. Aravagiri,
W.C. Wirshing
West Los Angeles VA. Medical Center, Brentwood Division, 11301 WTIshireBlvd., Los Angeles, CA 90073, U.S.A.
This presentation will review the current state of knowledge regarding the pharmacokinetics of long-acting depot neuroleptics and the clinical usefulness of monitoring plasma levels for these drugs. New data will be presented from our laboratory indicating that it requires approximately three months for patients started on a
et al., Pharmacopsychiat.
Monitoring
19:161-
166,19%.
service implementation
W.A. Hargreaves*,
T. Chouljian,
C. Coppolino,
in controlled
services trials
R. Hughes, R. Mance, J. Wade
Department of Psychiatry, University of California, SFGH Room 7M36, San Francisco, CA 94143-0852, USA
Manual-specified pharmacological and psychosocial treatment and other services are the norm for well designed controlled trials of interventions for patients with schizophrenia. Increased attention is being given to monitoring the actual implementation of services in controlled studies. We examined the ability of a simple instrument, the Community Program Philosophy Scale (CPPS), to detect differences among the five sites of the NIMH Treatment Strategies in Schizophrenia cooperative study, and between these five sites and a large group of other community programs that provide services to severely and persistently disabled persons with schizophrenia and other serious mental disorders. The CPPS was administered independently to several staff with client contact in each program. The 80 items of the CPPS form 20 4-item subscales that each have good internal consistency. A group of 12 subscales distinguished strongly among the set of comparison programs (subscales Outreach Orientation, Housing Assistance, Referral Advocacy, Emergency Access, Linking to Entitlements, Team vs Primary Therapist model, Longitudinality of Service, Family Orientation, Interest in Severely Mentally Ill Clients, De-emphasis of Psychotherapy, Substance Abuse Orientation, and Vocational Emphasis). Relative to the comparison programs, the cooperative study sites were tightly clustered on most of these subscales. The CPPS nevertheless showed sufficient sensitivity to detect statistically significant differences among the 5 cooperative study sites on 8 of the 20 subscales. It will be of interest to see whether these relatively subtle differences among the study sites have any relation to the relative cost effectiveness of the six treatments being compared, when this randomized controlled trial is completed.
Life events and prodromal
symptoms
in schizophrenia
M.I. Herz*, W.M. Glazer, M.A. Mostert Department of Psychiatry, SUNYat Buffalo, 462
GriderStreet, Buffalo, NyJ4215, USA.
We conducted a double-blind placebo controlled study of 101 schizophrenic outpatients comparing intermittent (antipsychotic medication given only when early symptoms of relapse appear) with maintenance medication. Since this was a double-blind study, when prodromal symptoms appeared, patients in both groups were given active antipsychotic medication openly. A variety of rating scales were administered at baseline, cross-sectionally every 6 months and during prodromal episodes, including measures of symptomatology, role functioning, life events, and family burden. This paper will describe the most frequent life events and prodromal symptoms found in the course of the study. It will also compare the frequency of life events and subjective reaction to them at baseline with those reported prior to the appearance of prodromal symptoms. The number of relapses and hospitalizations in each group will be reported. Knowledge about typical prodromal symptoms and life events which precede prodromal episodes should be of benefit in helping to prevent relapse and rehospitalization in schizophrenia.
Biologic indices of heterogeneity in schizophrenia: psychopathology and treatment outcome J. Lieberman*,
Relationship
to
D. Mayerhoff, A. Loebel, G. Degreef, D. Levy, J. Alvir
HilIside Hospital, Deparlment of Psychiatry, P.O. box 38, Glen Oaks, NY 11004, USA.
Biologic studies have consistently demonstrated brain morphologic, neurochemical and psychophysiologic pathology in schizophrenia. Efforts to determine the pathogenesis of these deficits and relate them to the phenomenology and course of schizophrenia in an effort to reduce the clinical heterogeneity of the disease, however, have been largely unsuccessful. Even the most robust biological abnormalities have been questioned
290 as to whether they reflect true pathology or the effects of illness chronicity, institutionalization and pharmacologic treatment. Consequently, we have initiated a study of never treated patients in their first episode of illness in a prospective longitudinal design to characterize biologic deficits and determine their clinical significance. Seventy-two patients (63% male, mean age 23 2 5.7 years) were ascertained when admitted to hospital for their first episode of schizophrenia and prior to neuroleptic treatment. Patients underwent clinical evaluation, MRI, methylphenidate challenge test and smooth pursuit eye movement exams under controlled conditions using standardized procedures. Patients received standardized treatment and were followed for up to three years with clinical evaluations. Rates of pathobiology for the measures used were: abnormal brain morphology 30%, psychotogenic response to methyl 61%, abnormal SPEM 43% (all rates were stat. sign. greater than normal control groups). Eighty-four percent of subjects achieved remission in a mean (SE)/median (SE) of 35.7 (7.4)/13 (3.1) weeks. The global outcomes of the sample were: 20% excellent, 21% good, 43% fair, 16% poor. Individual biologic abnormalities were significantly associated with poorer treatment response and outcome. When the combined effects of the biologic variables on treatment outcome were examined, the strength of the correlations (r) increased from .45 to 8 (P = .Ol). These and further results on the relationships between the biologic variables and psychopathology and treatment outcome will be presented and discussed.
Correlates
of course and outcome in first-episode
A. Loebel*, J. Lieberman,
schizophrenia
D. Mayerhoff, D. Jody, S. Szymanski, S. Geisler, M. Borenstein,
Hillside Hospital, Research Department, P.O. Box 38, Glen Oaks, Ny11004,
J. Ma Alvir
USA.
Various sociodemographic, phenomenologic and pathobiologic features have been associated with schizophrenic outcome. Major determinants of outcome remain unclear. Previous studies have been limited by retrospective evaluations, variations in illness chronicity and medication status, and heterogeneity in diagnosis and treatment, among other factors. In order to determine the relative contributions of premorbid functioning, age and mode of onset, and illness duration on various outcome measures, we studied 57 treatment-naive, first-episode schizophrenic patients as part of a larger, ongoing, prospective outcome study. Mean (5 S.D.) age on admission was 23.9 (* 5.7) years with a range of 14 to 40 years. The sample consisted of 41(72%) schizophrenics and 16 (28%) schizoaffective patients, diagnosed according to Research Diagnostic Criteria (RDC). Mean duration of symptoms on index admission was 1.4 years. All patients received structured diagnostic interviews and follow-up clinical and psychobiological assessments at regular intervals over a 3 year period. Standardized treatment algorithms were uniformly employed throughout their course. All patients were diagnostically assessed and subsequently followed by the same investigators. We propose that illness duration and premorbid adjustment in child and adolescent age ranges. Impaired premorbid adjustment was associated with shorter illness duration (prior to index hospitalization), but did not predict type of presenting psychopathology (positive psychotic vs negative symptoms). Using a Cox Proportional Hazards model of survival analysis, greater illness duration was found to predict increased time to remission in a younger age range (14 -24 years). Further potential predictors of course and outcome including age and mode of onset, illness subtype and severity, and presence of early deficit state symptoms, will be presented. Pathophysiologic implications of the lack of an illness duration effect in the older age range (25 -40 years) will be discussed. We conclude that early intervention in the course of schizophrenic illness, particularly in younger, premorbidly impaired patients, may assist in improving overall treatment outcome in first-episode schizophrenia. Further research will need to confirm and extend findings on the role of sociodemographic and clinical variables, as well as neuropsychologic and cerebral morphologic status of first-episode patients, in course and outcome of schizophrenia.
Plasma level monitoring
of depot neuroleptics
S.R. Marder*, T. Van Putten, M. Aravagiri,
W.C. Wirshing
West Los Angeles VA. Medical Center, Brentwood Division, 11301 WTIshireBlvd., Los Angeles, CA 90073, U.S.A.
This presentation will review the current state of knowledge regarding the pharmacokinetics of long-acting depot neuroleptics and the clinical usefulness of monitoring plasma levels for these drugs. New data will be presented from our laboratory indicating that it requires approximately three months for patients started on a